Alcohols, C11-15-secondary, ethoxylated

Endpoint summary

Description of key information

The eye irritation study results resulted in the  conclusion that Softanol 30 was not irritating to the eye RCC 1996, report 622438).
In an in-vitro skin irritation study it was concluded that  Softanol 30 is non-irritant (HLS 2010, PLZ0016). An in vivo skin irritation study with Softanol 50, a similar substance (5 ethoxy units in Softanol 50 instead of 3 ethoxy units in Softanol 30) concluded that it was not irritating to the skin. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 April 2010 to 19 April 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Conducted to draft OECD guidelines and to GLP.

Qualifier:

according to guideline

Guideline:

other: OECD Guideline For The Testing of Chemicals Draft proposal for a new guideline In Vitro Skin Irritation (OECD2009).

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Test Method B.46 In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

other: EPISKIN human epidermis skin constructs

Strain:

other: not applicable

Type of coverage:

other: not applicable

Preparation of test site:

other: not applicable

Vehicle:

unchanged (no vehicle)

Controls:

other: The negative control was sterile Dulbecco’s Phosphate Buffered Saline (DPBS) with magnesium and calcium. The positive control was 5% Sodium Dodecyl Sulphate (SDS) in distilled water.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 µL
- Concentration (if solution): 100%

Duration of treatment / exposure:

15+/-0.5 minutes

Observation period:

Not applicable

Number of animals:

Not applicable

Details on study design:

See any other information below.

Irritation / corrosion parameter:

other: other: viability percentage (vs. negative control)

Value:

64.7

Remarks on result:

other:

Remarks:

Basis: mean. Max. score: 100.0. (migrated information)

Table 1 EPISKIN Results

 

Sample	Tissue viability as percentage of mean OD negative control				Prediction MTT endpoint
	Replicate Tissues			Mean ± SD
	a	b	c
Negative Control	112.8	86.3	100.9	100.0 ± 13.3	Not applicable
Positive control	7.5	14.0	6.5	9.3 ± 4.1	Irritant
Softanol 30	51.9	63.8	78.5	64.7 ± 13.3	Non-irritant

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

It was concluded that the test substance, Softanol 30, with a mean tissue viability of 64.7 ± 13.3%, was predicted as a non-irritant to the skin.

Executive summary:

In an Episkin test realised according to the OECD guideline and in compliance with GLP, undiluted Softanol 30was applied for 15 minutes on human epidermis skin constructs and the effect on cell viability was evaluated (HLS 2010, PLZ0016). Appropriate positive and negative controls were used.

 

The tissue viability was 64.7+/-13.3% of the control value, and Softanol 30 was therefore not classified as irritant.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD GLP study realised on a similar structural substance.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Thomae GmbH Birkendorferstrasse 65, D-88397 Biberach / Riss
- Age at study initiation: 15weeks
- Weight at study initiation: male: 2.4kg, females: 2.6 - 2.7 kg
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum Pelleted standard Kliba 341 rabbit maintenance diet (batch 93/96).
- Water (e.g. ad libitum): ad libitum Community tap water from Itingen.
- Acclimation period: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-3
- Humidity (%): 40-70
- Air changes (per hr):10-15
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml

VEHICLE: N/A

Duration of treatment / exposure:

4hours

Observation period:

1, 24, 48, 72h

Number of animals:

1 male and 2 females

Details on study design:

TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: It was covered with a 3.0 ca x 3.0 cm patch of surgical gauze. The gauze was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with an elastic bandage. The test article was applied in such a position as to preclude oral ingestion after removal of the dressing.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Then the dressing was removed end the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.
- Time after start of exposure: 4h

SCORING SYSTEM: Similar to Draize scoring system

Irritation parameter:

overall irritation score

Basis:

animal #1

Remarks:

male

Time point:

other: 24, 48 and 72h

Score:

0

Max. score:

8

Irritation parameter:

overall irritation score

Basis:

animal #2

Remarks:

female

Time point:

other: 24, 48, 72h

Score:

0.67

Max. score:

8

Reversibility:

fully reversible within: 48h

Irritation parameter:

overall irritation score

Basis:

animal #3

Remarks:

female

Time point:

other: 24, 48, 72h

Score:

0

Max. score:

8

Irritant / corrosive response data:

SOFTANOL 50 showed a primary irritation score of 0.00 when applied to healthy intact rabbit skin.
Local signs (mean values from 24 to 72 hours) consisted or grade 0.22 erythema and grade 0.00 edema.
Very slight diffuse reddening was noted in one animal after 24 and 48 hours only.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred.
The bodyweight gain of all rabbits was within the normal range of variabliity.
No staining by the test article of the treated skin was observed.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Based on these observations and on the referred classification criteria, the test article SOFTANOL 50 is classified as 'not irritating' to rabbit skin.

Executive summary:

The primary skin irritation potential of the test article was investigated by topical application of 0.5 ml onto 6cm2 intact dorsal skin of each of three young adult New Zealand rabbits. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesions.

Under the conditions of this experiment, SOFTANOL 50 was found to cause a primary irritation score of 0.22 (Max 8.0) when applied to healthy intact rabbit skin.

Local signs (mean values from 24 to 72 hours) consisted of grade 0.22 erythema and grade 0.00 oedema.

The test article did not cause staining of the treated skin. The corrosive effects were noted on the treated skin of any animal at any measuring interval.

Based upon the referred classification criteria (EEC Commission Directive 93/21/EEC of April 27, 1993), the test article (SOFTANOL 50) is classified as 'not irritating' to rabbit skin.

Reference 3

Endpoint:

skin irritation: in vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation, other

Remarks:

An in vivo (already existing) study is available)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted according to internationally accepted guidelines and to GLP.

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Dr. Karl Tomae GmbH
- Age at study initiation: 14-15 weeks
- Weight at study initiation: male: 2.7kg; fem 2.6-2.8 kg
- Housing: individually in stainless steel cages with an automatic cleaning system, equipped with feed hoppers, drinking water bowls and wood for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Kliba 341 rabbit maintenance diet (batch 93/96) ad libitum from Kliba Muhlen AG, CH-4303 Kaiseraugst). Results of analysis for contaminants are included in this report.
- Water (e.g. ad libitum): Community tap water from Itingen, ad libitum.
- Acclimation period: four days under laboratory conditions after health examination. Only healthy animals were used for the study.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-3°C
- Humidity (%): 40-70%
- Air changes (per hr): 10 to 15 per hour
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: April 10, 1996 To: April 18, 1996

Vehicle:

unchanged (no vehicle)

Controls:

other: Each animal was only treated in left eye. The right eye was left untreated to act as control.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.1 ml undiluted

Duration of treatment / exposure:

once

Observation period (in vivo):

1, 24, 48 and 72 hours after administration

Number of animals or in vitro replicates:

1 male, 2 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none



SCORING SYSTEM:

CORNEA
Opacity: degree of density (densest area used for assessment)
No ulceration or opacity,0;
Scattered or diffuse areas of opacity (other than slight dulling of normal luster), details of iris clearly visible, 1 *;
Easily discernible translucent area, details of iris slightly obscured, 2 *;
Nacrous area, no details of iris visible, size of pupil barely discernible, 3*;
Opaque cornea, iris not discernible through the opacity, 4*.

IRIS
Normal, 0;
Markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperemia, or injection, any of these or combination thereof, iris still reacting to light (sluggish reaction is positive), 1 *;
No reaction to light, hemorrhage, gross destruction (any or all of these), 2 *

CONJUNCTIVE REDNESS (refers to palpebral and bulbar conjunctivae, excluding cornea and iris).
Blood vessels normal, 0;
Some blood vessels definitely hyperaemic (injected), 1;
Diffuse, crimson colour, individual vessels not easily discernible, 2;
diffuse beefy red, 3.

CHEMOSIS: lids and/or nictitating membranes
No swelling, 0;
Any swelling above normal (includes nictitating membranes), 1;
Obvious swelling with partial eversion of lids, 2;
swelling with lids about half closed, 3;
swelling with lids more than half closed, 4.

Maximum scores: Cornea: 4; Iris: 2; Conjunctival Redness:3; Conjunctival Chemosis:4
Maximum attainable score: 13
When present, corrosion of and/or staining of sclera and cornea by the test article were recorded and reported.

TOOL USED TO ASSESS SCORE: Eye examination were made with a Varta Cliptrix diagnostic lamp

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: 24h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: 24h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 24h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: 24h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: 24h

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24h

Score:

0

Max. score:

3

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: 24h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 24h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 48h

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 24h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: 24h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Softanol 30 showed a primary irritation score of 0.22 when applied to the conjuctival sac of the rabbit eye. No corrosion of the cornea was observed at any of the reading times.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the test and observation period, and no mortality occurred. Based upon the referred classification criteria the test article SOFTANOL 30 is classified as 'not irritating" to the eye.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

Based upon the GHS classification criteria the test article SOFTANOL 30 is Classified as 'not irritating" to the eye.

Executive summary:

In a primary eye irritation study realised according to the OECD guideline 405 and in compliance with GLP, 0.1ml of undiluted Softanol 30 was instilled into the conjunctival sac of left eye (right remained as control) of New Zealand rabbits (1 male, 2 females) for 1, 24, 48 and 72 hours (RCC 1996, report 622438). Eyes were not washed and animals then were observed for irritation at 1, 224, 48 and 72 hours. 

Softanol 30 showed a primary irritation score of 0.22 when applied to the conjuctival sac of the rabbit eye. No corrosion of the cornea was observed at any of the reading times.

Based upon the GHS classification criteria the test article SOFTANOL 30 is Classified as 'not irritating" to the eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Skin irritation

One in vitro study is available and valid. One in vivo study is available on a similar substance and supports the in vitro result.

Skin irritation was determined using the EPISKIN test method. The study was determined in accordance with OECD 439 Guideline For The Testing of Chemicals In vitro skin irritation (OECD 2009). The guideline states that the EPISKIN assay allows the prediction of both irritant and non-irritant substances and can thus be used as a stand alone method to be used as a replacement for the animal test. This test method is also included in COM regulation 440/2008/EC (2008) through the 1st Adaptation to Technical progress (ATP) to regulation 440/2008/EC, known as the test methods regulation.

In an Episkin test realised according to the OECD guideline and in compliance with GLP, undiluted Softanol 30 was applied for 15 minutes on human epidermis skin constructs and the effect on cell viability was evaluated (HLS 2010, PLZ0016). Appropriate positive and negative controls were used. The tissue viability was 64.7+/-13.3% of the control value, and Softanol 30 was therefore classified as not irritant.

The primary skin irritation potential of the test article was investigated by topical application of 0.5 ml onto 6cm2 intact dorsal skin of each of three young adult New Zealand rabbits (RCC 1996, 622440). The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values for each type of lesions. One female shown slight irritation at 24 hours, reversible within 48 hours. Under the conditions of this experiment, Softanol 50 was found to cause a primary irritation score of 0.22 (Max 8.0) when applied to healthy intact rabbit skin.

In the acute dermal toxicity study realised on rats (RCC 1997, 650518), some local effects were noticed, such as general erythema and scales on the backs of animals. Due to more stringent experimental conditions (longer exposure time, higher dose applied), those results cannot be used for classification purpose.

Eye irritation

One in vivo study is available and valid.

In a primary eye irritation study realised according to the OECD guideline 405 and in compliance with GLP, 0.1ml of undiluted Softanol 30 was instilled into the conjunctival sac of left eye (right remained as control) of New Zealand rabbits (1 male, 2 females) for 1, 24, 48 and 72 hours (RCC 1996, report 622438). Eyes were not washed and animals then were observed for irritation at 1, 224, 48 and 72 hours. 

Softanol 30 showed a primary irritation score of 0.22 when applied to the conjuctival sac of the rabbit eye. No corrosion of the cornea was observed at any of the reading times.

Based upon the GHS classification criteria the test article Softanol 30 is Classified as 'not irritating" to the eye.

 

Justification for classification or non-classification

Softanol 30 is not classified as an eye irritant. The eye irritation study in rabbits resulted in the conclusion that irritation found was minimal and fully reversible.

An in-vivo skin irritation study was performed on Softanol 30 and it was concluded that Softanol 30 is a non-irritant.